Dual action tofacitinib-loaded PLGA nanoparticles alleviate colitis in an IBD mouse model

Inflammatory bowel disease (IBD) affects over 7 million people worldwide, with current treatments like tofacitinib citrate (TFC) often limited by serious side effects, including increased risks of malignancy and heart complications. To tackle this, we developed a nanoparticle (NP) delivery system using poly(lactic-co-glycolic acid) (PLGA) to target drug release specifically to inflamed gut tissue.

Using nanoprecipitation, we optimised the synthesis of TFC-loaded PLGA nanoparticles and evaluated their performance *in vitro* under gastrointestinal conditions. This strategy combines the direct anti-inflammatory action of TFC with the local generation of anti-inflammatory short-chain fatty acids from PLGA degradation by colonic microbiota. In a mouse model of colitis, the TFC-loaded PLGA NPs significantly outperformed both free TFC and empty PLGA NPs in reducing weight loss, demonstrating improved efficacy through localised delivery and the combination of drug action with microbiota-mediated anti-inflammatory responses. These findings support the use of PLGA-TFC nanoparticles as a dual-action therapy for IBD, with the potential to reduce drug-related toxicity while enhancing treatment outcomes.

Read more about the study here.